In the past, the development of effective treatments for feeding disorders in cattle, sheep and goats has been spurred by a desire to maximize yields of meat and dairy products. Existing drug-based treatments (see, e.g., U.S. Pat. No. 4,761,426 issued to Martin, et al., and U.S. Pat. No. 4,405,609 issued to Potter), however, have the serious drawback of rendering products from treated animals unsalable for long periods under laws designed to protect consumers from harmful drug residues. Farmers, unhappy with the need to choose between low yields or unsalable products, have long sought the development of alternative, drug-free dietary treatments. The goals of drug-free dietary treatments are generally, improved growth and performance, and specially, appetite stimulation and reestablishment of the rumen bacterial populations necessary for proper digestion.
Much attention has been given in recent years to the use of certain microorganisms as dietary adjuncts in efforts to improve the growth and performance of livestock, and reestablishment of rumen bacterial populations. Such dietary cultures are known as probiotics or direct-fed microbials. (Gilliland, S. E., 8th Int'l. Biotech. Syn. Proc., Vol. 2, pp. 923-933 (1988)). Generally, the microorganisms of such probiotics are those that are expected to grow and/or function in the intestinal tract or rumen of the animal and can exert certain metabolic actions that influence the animal. Various microorganisms which have been considered for this type of usage include Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus fermentum, Lactobacillus casei, and Streptococcus faecium.
To derive maximum benefit from use of probiotics, the microorganisms must survive and grow in the intestine. It is thus imperative that the probiotic contain viable and active microorganisms at the time of consumption. The bacteria used as probiotics, therefore, must be stable during preparation and during storage prior to consumption.
The simplest approach to delivery of probiotics is to add cultures to animal feed. However, it appears that few direct-fed microbials are stable in feed for more than 3-5 days. (Aimutis, W. R., Feeds Management, Vol. 42, pp. 26-32 (1991)). Moreover, some feed contains antibiotics which are contrary to microbials stability. Yet other feed is pelleted, and most Lactobacillus species, which are predominant and beneficial intestinal species, are susceptible to the high temperatures, compression, aeration and mixing abrasion to which they are exposed during the pelleting process.
Another approach is to provide the bacteria themselves as a pellet or bolus. Many such bolus products are commercially available.
More recently, bolus or pellet formulations have been developed which include a combination of the bacteria and dry vitamin and trace mineral supplements, as nearly simultaneous administration in vivo of these components has been suggested as being highly beneficial to achieving the goals of appetite stimulation and bacterial population reestablishment. Many of these bolus formulations are available commercially. It has been found, however, that the supplements and bacteria are incompatible as the vitamin and mineral levels efficacious for livestock are toxic to the bacteria. As indicated previously, microorganisms are also sensitive to mixing abrasion, aeration, compression and high temperatures, all of which occur during conventional hard bolus production. Moreover, the bolus formulations also require binding, wetting and disintegrating agents, any or all of which may adversely affect the viability of the bacteria. Such bolus products, therefore, have limited shelf stability in that the population of viable bacteria is greatly reduced within about a week.
Thus, a persistent and vexatious problem, largely unattended by the prior art, is the lack of a method for simultaneously delivering incompatible substances in vivo to animals, particularly when one of the substances is a viable microorganism culture.
Various prior art methods of physical separation, e.g., encoating, encapsulation and microencapsulation, of nutritional supplements are known, however, none adequately address the preparation and storage requirements of sensitive direct-fed microbial agents. For example, conventional microencapsulation subjects bacteria to a number of potentially fatal packaging procedures and requires expensive materials, complex equipment, and carefully controlled environmental conditions. Polymeric microcapsules also require specific pH ranges or enzyme activities to effect release of their contents in vivo. These requirements often frustrate conventional laboratory assessment techniques and prevent effective nutrient release in animals whose rumen pH or enzyme balances have been disrupted by bacterial depopulation.
U.S. Pat. No. 4,695,466 to Morishita discloses a multiple-encapsulation method. The Morishita process includes successively encapsulating oil solutions or suspensions in soft capsules. Although the method of Morishita has potential for delivery of two components in a single vehicle, the use of oil carriers presents insurmountable obstacles to the delivery of bacteria and vitamin supplement components. It is unlikely that Morishita's soft outer capsules will be able to withstand common shipping, storage and administration conditions and also is unlikely applicable to commonly available microbial forms.
Despite recognition of the known drawbacks of prior art products, the art has not adequately responded to date with a method for delivery in vivo of the incompatible components, namely, direct-fed microbials and nutrient supplements nearly simultaneously to cattle, sheep and goats.